Multiple sclerosis (MS) is a chronic inflammatory disease that attacks myelin, the protective sheath that covers nerves and causes progressive and serious communication issues between the brain, central nervous system, and the rest of the body[1].
Currently, it’s estimated that over 2.3 million people worldwide, and over one million people in the US have a diagnosis of MS[2].
While there have been significant improvements in treatments designed to stabilize, delay, and even improve symptoms of MS, new and more effective treatments are needed to improve the long-term outcome associated with the condition.
One area currently being investigated as a potential therapeutic option for treating MS is the use of regenerative medicine, also known as stem cell therapy, and specifically treatment using mesenchymal stem cells (MSCs).
In this review of evidence from preclinical and clinical studies, Gugliandolo et al. examine studies involving the use of MSCs or their derivatives in vivo models of MS and patients affected by MS. The authors also examine and discuss the feasibility of autologous MSCs therapy for MS patients.
Specifically, and when assessed in terms of effectiveness when treating MS, the therapeutic potential of MSCs was associated with their differentiation capacity and paracrine effects, their ability to differentiate toward oligodendrocytes and express oligodendrocyte progenitor cell (OPC) markers, and their capacity for homing (moving towards the damaged area following chemical gradients).
As part of this review, the authors also examined the effectiveness of various sources of MSC in MS models, these sources included bone marrow MSCs (BM-MSCs), adipose tissue-derived MSCs (AD-MSCs), periodontal ligament stem cells (PDLSCs), skin-derived MSCs (S-MSCs), Wharton’s jelly-derived MSCs (WJ-MSCs), human umbilical cord MSCs (UCMSC), human amnion mesenchymal cells (AMCs), placental derived MSCs (PMSCs), and decidua derived MSCs (DMSCs). According to the research reviewed by Gugliandolo et al., all MSCs, regardless of where they were harvested from, demonstrated beneficial effects in the therapeutic treatment of MS.
Specifically, the results demonstrated that MSCs were able to produce some form of protective effects in reducing inflammatory cell infiltration, disease score, demyelination, and blood-brain barrier disruption.
A review of 29 phase 1 or 2 clinical trials registered on clinicaltrials.gov demonstrated that MSCs, regardless of the type and method of administration, demonstrated to be safe and absent of severe adverse effects with the majority demonstrating measurable improvements when used in MS patients.
While clinical trials demonstrated the safety of administration of MSC in MS patients, the authors were particularly interested in learning if autologous MSC transplantation presented some advantages over heterologous administration.
The authors of this review found that samples obtained from healthy controls and MS patients showed similar features, indicating the possibility of autologous stem cell therapy in MS patients. However, other studies found that MSCs obtained from MS patients exhibited a different transcriptional pattern and fewer immunosuppressive functions compared to healthy donor MSCs.
Gugliandolo et al. point out that limits to these experimental studies include the use of animals of a single gender, given that sex-dependent differences exist and the use of different MS models, different number of transplanted cells, different MSCs sources, and routes of administration. These limitations make it difficult to define the optimal treatment in terms of cell type, dose, and administration conditions.
The authors conclude that clinical trials demonstrate the safety and feasibility of MSCs treatment, and also some improvements, but more data on larger cohorts are required to establish their efficacy. Considering the controversial results pertaining to the features of MSCs derived from MS patients, the authors also call for additional research in order to conclusively determine the safety and efficacy of autologous MSCs therapy in MS patients.
When you live with chronic pain, almost any treatment option that offers relief can be tempting. Undergoing surgery for joint pain is a serious decision. Surgery comes with many risks, including potentially long and painful recovery times, and there is no guarantee that surgical treatments will resolve your pain. Before deciding whether surgery is the right step for you, take a moment to consider the following reasons why regenerative medicine, also known as stem cell therapy, might be an effective option.
Regenerative Medicine Is Minimally Invasive
The body’s natural response to surgical intervention is to create inflammation. Post-surgical swelling can be serious enough to prevent or limit movement and slow recovery time. Stem cell therapy is minimally invasive — involving only administrations at the injured site. A regenerative medicine provider first prepares the treatment area by applying a local anesthetic, which can minimize discomfort.
Instead of causing inflammation, stem cells have the ability to reduce swelling and support the body’s natural healing response. There is typically little or no downtime with stem cell therapy. Most patients can return to normal daily activity, following some post-procedure protocols, as soon as they leave the clinic.
Stem Cell Therapy Has Fewer Risks and Complications
No medical procedure is 100% risk-free. However, few complications are associated with stem cell therapy, especially when compared to surgery. The risks of even the most common surgical procedures include infection, damage to nerves or blood vessels, deep vein thrombosis, and adverse reactions to anesthesia.
Stem cell therapy does pose a few risks, most of which are mild and rare. Headache, nausea, swelling, or itching at the injection site are possible. Infection due to stem cell therapy is possible but extremely rare.
Regenerative Medicine Is More Cost-Effective
Stem cell therapy is not inexpensive, and most costs may have to be paid out of pocket since insurance, today, is still not covering treatments. Even with these considerations, the long recuperation and additional costs of surgery can add up. The costs associated with a possible long recuperation time, child care, and potentially lost wages may outweigh the costs of stem cell therapy considerably.
What Is Best for You?
Ultimately, each patient needs to do their individual research and weigh the pros and cons of any medical options before making an informed decision. Stem cell therapy is utilized to manage many conditions, including neurodegenerative and autoimmune conditions, and it serves as a potentially helpful approach in pain management contexts. Before deciding on a risky surgery, consult with a regenerative medicine specialist at Stemedix to learn more about your available options. If surgery is ultimately the best route for your recovery and wellness, stem cell therapy can still be an excellent post-surgery recovery tool.
Neurodegenerative conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) occur when neuron populations begin to diminish. There is currently no cure for these types of diseases, though clinical trials to explore various treatment options are ongoing. In particular, regenerative medicine, also known as stem cell therapy, is being heavily researched and has shown remarkable progress in controlling these conditions.
Types of Stem Cells
Stem cells serve as the foundation for every tissue and organ throughout the body. They are unspecialized but have the incredible ability to differentiate into virtually any cell type, as well as the power to self-renew.
Neurodegenerative conditions are characterized by neurons that progressively lose their function and structure, and eventually die off. Because stem cells are able to differentiate into multiple cell types, researchers have begun exploring whether they could replace or repair damaged neurons to control the progression of, or potentially even reverse the damage done by, these illnesses. Existing treatment options are limited, but many researchers are optimistic about stem cells’ potential.
Not all stem cells are the same. Here are the various types, some of which show more efficacy as a treatment for neurodegenerative disease than others:
Tissue-specific stem cells: These somewhat specialized stem cells can generate multiple organ-specific cells and are typically located in areas of the body that can self-replenish, such as the skin and blood.
Embryonic stem cells (ESCs): Located in blastocysts, ESCs are especially promising in neurodegenerative applications. Yet, they do pose some risks, including the risk of rejection. Due to their ability to differentiate into neurons, however, they continue to be studied as a potential therapy.
Induced Pluripotent Stem Cells (iPSCs): iPSCs are artificially derived from adult cells and programmed back to pluripotency, thereby allowing for an unlimited source of any cell type. While they are widely used for developing medications and disease modeling, further research must be done to refine the reprogramming process.
Mesenchymal Stem Cells (MSCs): MSCs can differentiate into several types of cells. Their self-renewal capabilities are far-reaching, making them an ideal candidate for therapies involving tissue repair. They may also be leveraged for cell transplantation in the treatment of neurodegenerative diseases.
Neural Stem Cells (NSCs): NSCs are derived from specific areas of the brain and are therefore specialized cells. They, too, are self-renewing and multipotent.
Types of Neurodegenerative Conditions Regenerative Medicine can Help Manage:
While researchers are uncovering new findings on how stem cells can treat neurodegenerative conditions nearly every day, there has already been progress. Here are some of the conditions stem cell therapy has been used to manage:
Parkinson’s Disease (PD): One hallmark characteristic of PD is the decline of dopamine, caused by the destruction of dopamine-producing brain cells. As dopamine decreases, symptoms such as muscle tremors, challenges with movement, and difficulty thinking arise. Now, researchers have found that stem-cell-derived dopaminergic neurons — in particular, those created through ESCs and iPSCs — could hold success in replacing the destroyed brain cells in individuals with PD.
Alzheimer’s Disease: Through the use of stem cell therapy, researchers at Columbia University have refined the protocol for a unique process of converting skin cells into brain cells. This option streamlines the process of creating neurons to replace those which have become damaged by Alzheimer’s disease. In their research, the cells were able to receive signals just as normal neurons would.
ALS: ALS has proven remarkably challenging to study, as there are many potential causes and therapies may therefore only be effective on specific patient populations. Moreover, the motor neurons, which are directly impacted by the condition, couldn’t be acquired in large enough numbers to study. Now, however, Harvard researchers have been able to derive mature cells that can be manipulated back into stem cells from ALS patients, opening up new doors for studying potential therapies to treat the condition.
While there is more ground to cover before stem cell therapy for neurodegenerative conditions can become mainstream, promising research is consistently being published. Moving forward, it’s likely that stem cells will hold the answer to viable management options for these and other challenging conditions.
According to the CDC, stroke continues to be a major cause of serious disability for adults. It is also estimated that nearly 800,000 people in the United States have a stroke each year[1]. While 80% of those experiencing a stroke survive for at least one year following the event, more than 70% will continue to experience long-term disabilities.
Stroke is divided into three distinct phases: acute, subacute, and chronic phases. The acute phase of stroke occurs within 24 hours of the actual ischemic event. The subacute phase starts at 24 hours and lasts up to 3 months. The chronic phase of stroke, by definition, starts at 3 months.
While stroke patients tend to see some response to rehabilitation efforts occurring in the chronic phase, they tend to quickly plateau, leaving many with serious chronic neurological and functional disabilities. To date, there are no approved treatments for the chronic phase of stroke.
For the purposes of this study, Steinberg et al. report the two-year outcomes of their phase 1/2a study examining chronic stroke patients after implantation of mesenchymal stem cells (MSCs). This study specifically examined the outcomes of 18 patients who were at least 6 months post-stroke onset and had chronic motor deficits secondary to the nonhemorrhagic stroke.
At the 1-year point of this study, the authors reported the implantation of bone marrow-derived MSCs (BMD MSCs) was generally safe, well-tolerated, and associated with significant improvement in clinical outcomes.
There were no correlations between improvement in clinical outcomes and cell dose, baseline patient age, or baseline stroke severity. However, two years after implantation of MSCs, those enrolled in this study experienced significant improvement in motor impairment scales as indicated by a number of scores, including the ESS, NIHSS, F-M total, and FMMS scores.
Although all enrolled patients experienced at least one Treatment-Emergent Adverse Event (TEAE), with headache and nausea being the most common, 94.4% of the TEAEs were determined to be unrelated and no one withdrew from the study.
Interestingly, the authors reported that there also appears to be a significant correlation between the size of newly appearing transient lesions primarily in or adjacent to the premotor cortex – a finding that remained consistent at month 12 and month 24 of this study.
While Steinberg et al.’s reported findings are encouraging, the authors point out that the small scale and uncontrolled study design mean the findings should also be interpreted with caution.
Steinberg et al conclude that their findings associated with this completed, open-label, single-arm phase 1/2a study was consistent with the data at the 1-year point and indicated that treatment of chronic stroke with BMD MSCs after 2 years continued to be safe and was associated with sustained and significant improvements in clinical outcomes.
Given the findings of this study, the authors highlight the potential of MCSs, and specifically SB623 cells used in this study, as a potential treatment for patients with chronic ischemic stroke.
Current estimates indicate that kidney disease currently affects over 37 million US adults and over 10% of the global population[1]. Characterized by gradual loss of function, kidney disease generally progresses over time and culminates in the inability to remove waste and excess fluid from the blood[2].
Often demonstrating little to no symptoms in its early stages, chronic kidney disease tends to demonstrate increasing and dangerous symptoms as the condition advances.
To date, treatment for chronic kidney disease has been centered around causal control as a way of slowing the progression of the condition. However, these therapeutic treatment efforts, including multidrug therapy, have demonstrated an inability to reverse the condition from progressing to end-stage renal disease (ESRD) and requiring additional therapy, dialysis, or kidney transplantation.
Considering the high cost and disruption to normal life function associated with dialysis and the severe shortage of viable kidney donors, neither dialysis nor transplant has proven to be ideal or often recommended treatment strategies. As a result, there has been renewed interest in new and more effective therapeutic options to alleviate, cure, or prevent kidney disease and to improve a patient’s survival and quality of life.
Evaluating the numerous and growing therapeutic applications associated with stem cells’ ability for self-renewal, proliferation, and differentiation, Liu et al.’s review explores the potential benefits offered toward improving renal function and supporting structural repair in those afflicted with kidney disease.
Despite the promising benefits of using stem cells to kidney repair and disease treatment demonstrated through prior preclinical study, the authors point out that certain ethical issues regarding the origin of stem cells, and specifically embryonic stem cells (ESCs) need to be addressed and overcome before clinical application of SCs.
Regardless of the stated drawbacks, Liu et. al concludes that the existing evidence demonstrates that stem cell therapy appears to be a clinically viable alternative for kidney disease, specifically for restoring normal kidney function and for progressing understanding about tissue regeneration, drug screening, and disease modeling.
Although stem cells demonstrate promise in this regard and while the immunomodulatory properties of mesenchymal stem cells (MSCs) appear to make them the most promising SC for treating kidney disease, the authors also point out that further research is needed before definitively concluding which source of SC is best suited for this application.
As a result of this review, and in an effort to realize these findings into clinical applications in the future, the authors call for larger rigorously designed clinical trials to further assist in determining the clinical efficacy of SC therapy in kidney disease – including the appropriate selection of cell types, number of SCs required, and the appropriate route of administration.
According to recent data from the CDC, an estimated 30 million Americans currently have type 2 diabetes mellitus (T2DM), and another 88 million are considered to be prediabetic[1].
Occurring most often as a result of being overweight and/or sedimentary and often resulting in severe kidney, heart, or vision issues, T2DM has demonstrated to be difficult to treat, often resulting in life-long insulin therapy as the primary method of treatment.
Considering the negative impacts associated with insulin treatment, and T2DM in general, Liu, et al.’s research explores the potential of specific mesenchymal stem cells (MSCs) in the treatment of the condition.
Recently, stem cell therapy has been shown to be beneficial in improving glycemic control and beta function. Building off of these findings, Liu, et. al designed this study to specifically examine the efficacy and safety of Wharton’s Jelly mesenchymal stem cells transplantation (WJ-MSC) as a therapeutic option for those with T2DM.
The authors’ single-center phase I/II study involved observing 22 patients with T2DM for 12 months after receiving two injections of WJ-MSC (one intravenously and one intrapancreatic endovascularly). Over the course of the 12-month observation period, the participants were monitored with primary endpoints observed including changes in the levels of glycated hemoglobin and C-peptide and secondary endpoints including insulin dosage, fasting blood glucose, post-meal blood glucose, inflammatory markers, and T lymphocyte counts.
At the conclusion of this study, Liu et al. found that both glycated hemoglobin and fasting glucose levels demonstrated a progressive decline after WJ-MSC transplantation and over the course of the 12-month follow-up period, the suggested potential of long-lasting effects of the WJ-MSC treatment. Researchers also observed a general improvement in fasting C-peptide levels. Secondary endpoint observations over the course of the 12-month follow-up included improved beta-cell function and reduced markers of systemic inflammation and T lymphocyte counts.
While there were no significant adverse observed effects associated with either of the WJ-MSC injections, the authors did note isolated and separate incidences of mild fever, nausea, and headache in a very small number of participants – all of which spontaneously resolved within a week of onset. The authors also noted a temporary decrease in levels of C-peptide and beta-cell function one month after treatment, possibly related to the intrapancreatic endovascular injection. As a result of these observations, the authors call for further investigation of the safety of intrapancreatic endovascular delivery of WJ-MSC.
As a result of this research, Liu et al. concluded that their findings suggest the possible therapeutic potential of WJ-MSC transplantation for treatment of T2DM and specifically with improved beta-cell function, systemic inflammation, and immunological regulation. The authors also call for further large-scale placebo-controlled clinical studies to fully understand the safety and efficacy of WJ-MSCs in the treatment of T2DM. Source: “PMC – NCBI.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055092/
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